Neutrophils



Neutrophils


Diane C. Farhi



This section focuses on acquired and reactive neutrophil changes in the peripheral blood and bone marrow. Constitutional disorders of neutrophils are discussed in Chapter 4. Clonal disorders of neutrophils are discussed in later chapters.

The major sections below are neutrophil disorders in the peripheral blood, neutrophil disorders in the bone marrow, and morphologic abnormalities of neutrophils.


NEUTROPHIL DISORDERS IN THE PERIPHERAL BLOOD

Conditions discussed in this section include acquired neutropenia, pseudoneutropenia, acquired cyclic neutropenia, reactive neutrophilia, leukemoid reaction, and leukoerythroblastosis (Table 6.1).


Acquired Neutropenia

Acquired neutropenia may be transient, persistent or chronic, or cyclic. Transient neutropenia is a common finding in viral infection, and usually resolves within a few days to weeks without severe complications. Persistent or chronic neutropenia is a more serious finding, prompting a more thorough search for etiology and therapy.

Acquired neutropenia has been reported in a variety of populations, from neonates to older adults. The clinical course ranges from benign (i.e., infection-free) to serious or fatal owing to life-threatening infection.

Numerous mechanisms have been implicated in the pathogenesis of chronic neutropenia (Table 6.2) (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34). These include autoimmunity, alloimmunity, idiosyncratic and dosedependent drug reactions, overwhelming infection, premature birth, and neutrophil sequestration. Transplacental passage of maternal antibodies may cause autoimmune or alloimmune neutropenia in the neonate. Neutrophil sequestration has been reported in pneumonia and sepsis.

Conditions associated with chronic neutropenia include prior cyclic neutropenia, drug reactions, sepsis, bacterial and viral infection, gold therapy, antibiotic therapy (which may both provoke and ameliorate neutropenia), antithyroid therapy, histamine 2 (H2)-receptor antagonist therapy, colchicine intoxication, Epstein-Barr virus infection, parvovirus B19 infection, Behçet disease, Sjögren syndrome, T-cell neoplasms (especially T-cell large granular lymphocytic leukemia), hairy cell leukemia, acute myeloid leukemia, and replacement of bone marrow by fibrosis, bone, or metastatic malignancy. In many cases, no pathogenetic mechanism or underlying condition is apparent and the disorder is termed idiopathic.

In one recent study, among adults with chronic neutropenia 34% were found to have no identifiable etiology; exposure to chemical agents was the etiology in 17%; infectious diseases in 9%; autoimmune diseases in 9%; hematological diseases in 9%; thyroid disorders in 8%; ethnic neutropenia in 7% (discussed further below); drug-related neutropenia in 2%; and iron deficiency in 2% (20). The majority of cases—those not deemed idiopathic or resulting from chemical exposure—recovered with specific therapy. Many others have been reported to respond to treatment with antibiotics, granulocyte colony-stimulating factor, and’or immune modulators; some show spontaneous remission.

The peripheral blood shows an absolute neutrophil count (ANC) of less than the normal laboratory range, usually less than 1.5 × 109‘L. Monocytosis is present in some cases. The platelet count may be decreased. Cases with neutropenia, thrombocytopenia, and anemia are discussed with aplastic anemia. Recovery from neutropenia may be attended by neutrophilia or a neutrophilic leukemoid reaction.

Bone marrow aspirate smears and histologic sections show variable cellularity. In most cases, neutrophils and precursors are increased, often with a pronounced increase in metamyelocytes, myelocytes, and promyelocytes (left shift). Phagocytosis of neutrophils by bone marrow macrophages has rarely been reported. Mature segmented neutrophils and band forms may be reduced or virtually absent, a condition termed granulocytic maturation arrest. This may be a misnomer because it is not clear in most cases whether the lack of mature neutrophils is actually owing to impaired maturation or to rapid clearance and destruction. Some cases of neutropenia show marked reduction in the entire neutrophil series, or pure white cell aplasia (see below).

The differential diagnosis includes constitutional neutropenia and pseudoneutropenia. Constitutional neutropenia
is more fully discussed in Chapter 4. Pseudoneutropenia is discussed later.








TABLE 6.1 Reactive Neutrophil Disorders





























Neutrophil Disorders in the Peripheral Blood


Acquired neutropenia


Acquired cyclic neutropenia


Pseudoleukopenia (pseudoneutropenia)


Reactive neutrophilia


Neutrophilic leukemoid reaction


Leukoerythroblastosis


Pseudoleukocytosis (pseudoneutrophilia)


Neutrophil Disorders in the Bone Marrow


Neutrophilic hypoplasia and pure white cell aplasia


Neutrophilic hyperplasia


Neutrophilic maturation arrest


Other Morphologic Abnormalities of Neutrophils


In neonates and young children with severe infections, the differential diagnosis includes constitutional neutropenias, primarily Kostmann syndrome and severe congenital neutropenia, which may be difficult to distinguish from acquired neutropenia. Clinical history and course are important in resolving this differential diagnosis.

In older patients without severe infection, the differential diagnosis includes benign hereditary (ethnic, familial) neutropenia, an important constitutional neutropenia frequently mistaken for true neutropenia. Benign hereditary neutropenia is not a disorder, but simply a lower normal range for the ANC found in some ethnic groups (Table 6.3). Lower normal ranges for ANC are found in some groups of Africans, African-Americans, Arab Jordanians, and African and Yemenite Jews. The lower limit of normal ANC in such groups is about 1.2 × 109‘L, possibly a little less.

This finding is of no clinical significance and should not be confused with true neutropenia, which may be complicated by serious infections. Individuals with benign ethnic neutropenia may be unnecessarily subjected to repeated laboratory testing, including bone marrow examination, in a futile effort to determine the cause of apparent neutropenia.


Acquired Cyclic Neutropenia

Acquired cyclic neutropenia is an uncommon disorder with variable characteristics (Table 6.4) (35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50). It may be accompanied by cyclic fluctuation of other cell counts. It shows a wide range of cycle length among individuals, as well as variable cycle length in an individual patient. Additional findings may include cyclic variation in the number and maturation of bone marrow granulocytic precursors and cycling of body temperature.








TABLE 6.2 Conditions Associated with Acquired Neutropenia






















































































Nonneoplastic Conditions


Bone marrow replacement by metastatic malignancy, fibrosis, bone, etc.


Chemical agent exposure


Copper deficiency


Drug therapy



Antibiotics



Antithyroid medication



Colchicine



Gold



Histamine 2 (H2)-receptor antagonists



Neuroleptic drugs


Folate and vitamin B12 deficiencies


Infection



Bacterial infection



Epstein-Barr virus infection



Hepatitis virus infection



Parvovirus B19 infection



Sepsis


Immune-mediated disorders



Autoimmune neutropenia



Alloimmune neutropenia



Behçet disease



Sjögren syndrome


Iron deficiency


Neonatal conditions



Premature birth



Transplacental passage of maternal antibodies


Prior cyclic neutropenia


Thyroid disease


Neoplastic Conditions


Prodrome to acute myeloid leukemia


Hairy cell leukemia


T-cell neoplasms


Conditions associated with acquired cyclic neutropenia include autoimmune neutropenia, ankylosing spondylitis, Crohn disease, phenylbutazone therapy, common variable immunodeficiency, myeloproliferative disorders, myelodysplastic syndrome, acute lymphoblastic leukemia, and T-cell neoplasms.








TABLE 6.3 Populations with Benign Ethnic Neutropenia











Africans


African-Americans


Arab Jordanians


African and Yemenite Jews










TABLE 6.4 Conditions Associated with Acquired Cyclic Neutropenia



























Nonneoplastic Conditions


Autoimmune neutropenia


Ankylosing spondylitis


Crohn disease


Phenylbutazone therapy


Common variable immunodeficiency


Neoplastic Conditions


Myeloproliferative disorders


Myelodysplastic syndromes


T-cell large granular lymphocytic leukemia


Adult T-cell leukemia’lymphoma


Acute lymphoblastic leukemia


Patients suffer during the nadir of the absolute neutrophil count (ANC) with fever, mouth ulcerations, and infections. The peripheral blood shows an ANC below the lower limit of normal, sometimes profoundly low. The bone marrow may show cyclic variation in the number of neutrophilic precursors.

The outcome may be persistent cycling, disappearance of the disorder, or eventual development of persistent agranulocytosis. Acute leukemia is not a complication, as it is in constitutional cyclic neutropenia.

The differential diagnosis includes constitutional cyclic neutropenia (discussed in Chapter 4), a disorder which may be difficult to distinguish from the acquired condition, especially in young patients.


Pseudoneutrophilia

Pseudoneutropenia, or pseudoleukopenia, or is an artifactual reduction in the white blood cell count or absolute neutrophil count caused by neutrophil agglutination or, rarely, overfilled blood vacuum tubes (Table 6.5) (51, 52, 53, 54, 55, 56, 57, 58).

Neutrophil agglutination is apparently mediated by immunoglobulin G or M antibodies against neutrophil surface antigens. Underlying conditions include high-dose gammaglobulin therapy, herpes simplex infection, pneumonia caused by Mycoplasma pneumoniae and other organisms, hepatic disorders, vasculitis, and colon carcinoma. Some subjects with neutrophil agglutination appear healthy. Agglutination may disappear after treatment of the underlying condition, if one is present.








TABLE 6.5 Conditions Associated with Pseudoneutropenia



















IgG or IgM antibodies against neutrophil surface antigens


High-dose gamma-globulin therapy


Herpes simplex infection


Pneumonia caused by Mycoplasma pneumoniae and other organisms


Hepatic disorders


Vasculitis


Colon carcinoma


Overfilled blood vacuum tubes


The physical conditions for neutrophil agglutination vary. In some cases, agglutination occurs with ethylenediaminetetraacetic acid (EDTA), sodium citrate, lithium heparin, and’or acid citrate dextrose, at room temperature but not at 37°C. In other cases, agglutination occurs only with EDTA, both at both room temperature and at 37°C.

Laboratory studies may show pseudothrombocytopenia as well as pseudoneutropenia.

The peripheral blood smear shows aggregates of neutrophils ranging from 2 to 80 or more cells. In some cases, platelet satellitism around neutrophils is also found.


Reactive Neutrophilia

Reactive neutrophilia is a common peripheral blood finding (Table 6.6) (59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102). The white blood cell (WBC) count and
absolute neutrophil count (ANC) exceed the upper limit of normal for the laboratory, approximately 11 × 109‘L and 8 × 109‘L, respectively.

Only gold members can continue reading. Log In or Register to continue

Stay updated, free articles. Join our Telegram channel

Jun 19, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Neutrophils

Full access? Get Clinical Tree

Get Clinical Tree app for offline access